Radioactive therapeutic fastening instrument

ABSTRACT

An instrument used for brachytherapy delivery in the treatment of cancer by radiation therapy including a handle having first and second handle actuators; an end effector; and an instrument shaft that connects the handle with the end effector. The end effector has first and second adjacent disposed staple mechanisms that each retain a set of staples. The first mechanism is for holding standard staples in a first array, and dispensing the standard staples under control of the corresponding first handle actuator. The second mechanism is for holding radioactive source staples in a second array, and dispensing said radioactive source staples under control of the corresponding second handle actuator. A holder is for receiving the first and second mechanisms in a substantially parallel array so that the standard staples close the incision at a surgical margin while the source staples are secured adjacent thereto.

RELATED APPLICATIONS

This application is a continuation-in-part (CIP) of U.S. Ser. No.12/462,042 filed on Jul. 28, 2009 which is a divisional of U.S.application Ser. No. 11/732,315, filed on Apr. 3, 2007 priority for thisapplication is hereby claimed under 35 U.S.C. §119(e) to commonly ownedU.S. Provisional Patent Application No. 60/792,733 which was filed onApr. 18, 2006. The content of all of the aforementioned applications arehereby incorporated by reference herein in their entirety.

TECHNICAL FIELD

The present invention relates to an improved method and system forapplying a radioactive source to a tissue site. More particularly, thepresent invention pertains to an improved delivery system based upon theincorporation of a radioactive seed by fastening means, such as asurgical staple. More specifically, the present invention pertains to animproved brachytherapy delivery system for applying a radioactive sourceto a tissue site. Even more particularly the present invention relatesto a new instrument construction wherein a single stapler instrument isused for precisely applying both standard surgical staples, as well asbrachytherapy source staples relative to a surgical margin.

BACKGROUND DISCUSSION

The incidence of lung cancer has been rising over the last half century,although the rate has decreased somewhat over the last decade. TheAmerican Cancer Society estimates the number of new cases in 2006 toexceed 174,000. Lung cancer is the leading cause of cancer deaths in theUnited States among both men and women, claiming more lives than colon,prostate and breast cancer combined.

Non-small cell lung cancer (NSCLC) is the most commonly-diagnosed formof the disease, affecting 4 out of 5 patients. In North America, 75% ofpatients are present with the early-stage (T1, T2) disease. In mostcases, early stage NSCLC can be treated successfully with surgery if thecancer has not spread beyond the chest. Surgical resection is thedefinitive treatment and lobectomy is the procedure of choice. Lobectomyis the most common type of lung cancer surgery, involving removal of anentire lobe of one lung. For these early stage NSCLC patients, lobectomyyields a 5-year survival rate of 65-77%. Locoregional recurrence occursin 28% of T1N0 tumors submitted to thoracotomy, with the highest initialfailure rates detected in the ipsilateral hemithorax. Unfortunately,some patients with this disease are poor candidates for lobectomy due topoor pulmonary health or other medical issues.

Stage I NSCLC patients with compromised cardiopulmonary status mayundergo limited surgical resections in an attempt at lung preservationwhile achieving adequate resection margins. However, lesser resectionshave been associated with an increased risk of local recurrence, evenfor small peripheral tumors. Nonetheless, limited resection is viewed asan acceptable alternative for patients with poor physiologic reserve orof advanced age.

Though sublobar resection alone is associated with an increasedincidence of post-operative disease recurrence, it is still advocatedfor high risk patients in the absence of a good alternative. Externalbeam radiation therapy has been used successfully to reduce the risk oflocal recurrence in these compromised patients. However, external beamradiation therapy further reduces pulmonary function because itgenerally requires the beam to pass through normal lung to reach thetarget lesion. Some studies suggest that adding brachytherapy to theregimen can make a dramatic difference in outcomes.

Brachytherapy has a long history of use in the treatment of lung cancerpatients. Prior studies have shown improved local control using Iodinepermanent implants as a radiation boost for Stage III NSCLC withparaspinal or chest wall involvement. Intraoperative brachytherapy hasbeen shown to be an effective therapeutic modality for patients unableto undergo a surgical lobectomy; it is an alternative to external beamirradiation for patients who cannot tolerate further loss of lungfunction.

D'Amato et al. at Allegheny General Hospital reported favorable resultsusing a brachytherapy technique to implant ¹²⁵Iodine seeds for improvinglocal control in patients undergoing thoracoscopic wedge resection forperipheral stage I lung cancer. A series of fourteen patients withnon-small cell cancer and significant impairment in cardiopulmonaryfunction having small peripheral solitary pulmonary nodules underwentvideo-assisted thoracoscopic wedge resection and intraoperative¹²⁵Iodine seed brachytherapy. At a mean follow-up of 7 months (range, 2to 12 months), there were no cases of significant radiation pneumonitisor local recurrence. They concluded intraoperative brachytherapy appearsto be a safe and efficient alternative to external-beam radiationtherapy when adjuvant radiotherapy is considered following therapeuticwedge resection of stage I (T1N0) lung cancers.

Lee et al. at Tufts New England Medical Center reported the results oflimited resection for non-small cell lung cancer and the observed localcontrol achieved with the implantation of ¹²⁵Iodine brachytherapy seeds.Their series consisted of 35 patients who were deemed not to becandidates for a lobectomy or pneumonectomy due to compromised pulmonaryfunction or cardiac indication. These candidates underwent wedgeresection (32 patients), segmental resection (2 patients) and lobectomy(1 patient). All patients received ¹²⁵Iodine seed placement along theresection margin to deliver a dose of 125 to 140 Gy at a 1-cm depth.Their results suggest that limited resection is a reasonable alternativeto nonoperative management of lung cancers for compromised patients,particularly those with stage IA lung cancers. The implantation of¹²⁵Iodine brachytherapy seeds is effective in reducing the recurrence atthe resected lung margin.

Birdas et al. reported further on the work of the Allegheny GeneralHospital group. They had previously shown that intraoperativebrachytherapy decreased the local recurrences associated with sublobarresections for small stage IA NSCLC. In this report, they presented theoutcomes of sublobar resection with brachytherapy compared withlobectomy in patients with stage Ib tumors. They retrospectivelyreviewed 167 stage IB NSCLC patients: 126 underwent lobectomy and 41sublobar resection with ¹²⁵Iodine brachytherapy over the resectionstaple line. Endpoints were perioperative outcomes, incidence ofrecurrence, and disease-free and overall survival. Patients undergoingsublobar resections had significantly worse preoperative pulmonaryfunction. Hospital mortality, nonfatal complications, and median lengthof stay were similar in the two groups. Median follow-up was 25.1months. Local recurrence in sublobar resection patients was 2 of 41(4.8%), similar to the lobectomy group: 4 of 126 (3.2%; p=0.6). At 4years, both groups had equivalent disease-free survival (sublobar group,43.0%; median, 37.7 months; and lobectomy group, 42.8%; median 41.8months, p=0.57) and overall survival (sublobar group, 54.1%; median,50.2 months; and lobectomy group, 51.8%; median, 56.9 months; p=0.38).They concluded that sublobar resection with brachytherapy reduced localrecurrence rates to the equivalent of lobectomy in patients with stageIb NSCLC, and resulted in similar perioperative outcomes anddisease-free and overall survival, despite being used in patients withcompromised lung function. They recommend the addition of intraoperativebrachytherapy to sublobar resections in stage Ib patients who cannottolerate a lobectomy.

These early indications of the efficacy of brachytherapy used inconjunction with sublobular resection for compromised patients have setthe stage for a planned national, multi-center clinical trial by theAmerican College of Surgeons Oncology Group and NIH. This Phase IIItrial, identified as NCT00107172, is currently enrolling patients. Thesestudies and the Phase III clinical trial clearly demonstrate thepotential for intraoperative brachytherapy for those non-small cell lungcancer (NSCLC) patients with compromised cardiopulmonary status who arenot candidates for lobectomy.

One main problem facing this technique is in the ability to preciselydeliver the brachytherapy seeds intraoperatively to achieve the properdose distribution and minimize the radiation dose to the cliniciansperforming the procedure.

Under one practice, Pisch et al. have reported on a technique in whichloose seeds were manually delivered via a Mick™ applicator. Althoughthey did not describe the surgical procedure, they did state that theymade multiple passes in the lung parenchyma. Consequently, thisprocedure would not have been possible through a thoracoscopy port,which would be a potential problem in patients with chronic obstructivepulmonary disease. They also did not discuss seed migration, which wouldbe expected to be a significant issue.

Chen et al. developed an intraoperative technique utilizing vicryl meshimbedded with ¹²⁵Iodine radioactive seeds for thoracoscopic placementover the tumor bed and staple line after video-assisted thoracoscopicresection. ¹²⁵Iodine seeds, spaced 1 cm apart, were embedded into ahollow vicryl suture material. These seeds were attached to a sheet ofappropriately sized vicryl mesh with sutures and/or surgical clips ateach end. The spacing between rows was adjusted to deliver a dose of100-120 Gy at 0.5 cm. Radiation protection was achieved during thispreparatory step by the use of a custom leaded-plexiglass, autoclavableshield within which the mesh was assembled. The ¹²⁵Iodine vicryl meshwas then inserted through the thoracoscopy port and sutured over thetumor bed and resection line. As the radioactive mesh was implanted withvideo assistance over a relatively flat resection surface, it would layover the surgical bed without any source overlap. Postoperative,orthogonal simulation films were obtained for placement verification andcomputer dosimetry. Although this procedure solves the problem of seedmigration, it presents other difficulties. As shown in the photographsof the paper, delivery of the mesh through the thoracoscopy port is adifficult procedure and one with appreciable dose to the physician.Proper positioning of the mesh in relation to the surgical margin iscritical and difficult. Because the seeds are secured in the mesh priorto insertion, they rely on the proper positioning of the mesh inrelation to the target to achieve the desired dose distribution. FIG. 1illustrates this mesh/seed arrangement.

Lee et al. have reported on a technique that solves some of theseproblems. In this technique, patients undergoing wedge resection have anincision as small as possible, sometimes as small as 5 cm in length. Theresection is carried out using either a linear gastrointestinal stapleror an endostapler. They intend to achieve a minimum gross margin>1 cmaround the tumor.

Strands of ten ¹²⁵Iodine brachytherapy seeds, embedded in polyglactin910 suture with 1 cm spacing were affixed along the resection margin or0.5 cm on either side of the margin, depending upon the source strength,length of the resection margin, and the number of seeds available. Inmost cases, from one to three strands were affixed on both sides of theresection margin over its entire length, utilizing interrupted suturesof 3-0 silk spaced approximately 2 cm apart. Whenever an insufficientnumber of seeds were available to cover the entire resection margin withparallel strands, the most peripheral portion of the resection marginwas affixed with a single strand, and the more central portion affixedwith parallel strands on either side of the stapled margin. FIG. 2 showsan example of this technique. Source strength was chosen to deliver acombined radiation dose of 125-140 Gy at a depth of 1 cm. FIG. 2 shows aportion of lung in which a wedge resection has previously been carriedout. Each limb of the wedge resection is approximately 6 cm in length.Shown is how two multi-seed strands would be affixed to the margin. Themost peripheral seeds are placed directly in the margin, and the deeperportions of the wedge have two strands of seeds affixed to the lungspaced approximately 1 cm apart or 0.5 cm from the resection margin.Simple 3-0 silk sutures may be used to hold the strands in place.

This technique has a better possibility of positioning the seeds at theappropriate position relative to the resection margin. However, theradiation dose to the hands of the radiation oncologist/surgeon issignificant. Even through the use of relatively thin lead gloves, thereduction in dose is limited. The use of thicker, more heavily shieldedlead gloves limits the dexterity sufficiently as to be impractical.

To address this problem, Pisch et al. have reported on an evaluation ofthe feasibility of using the da Vinci robotic system (IntuitiveSurgical) for radioactive seed placement in the wedge resection margin.Their study was of pigs' lungs. Video-assisted thoracoscopic wedgeresection was performed in the upper and lower lobes in pigs. Dummy¹²⁵Iodine seeds embedded in absorbable sutures were sewn into theresection margin with the aid of the da Vinci robotic system withoutcomplications. In the “loop technique,” the seeds were placed in acylindrical pattern; in the “longitudinal,” they were above and lateralto the resection margin. Orthogonal radiographs were taken in theoperating room. Calculated doses at 1 cm ranged from 70 Gy to 107 Gydepending upon the technique. They concluded that robotic technologyallows direct placement of radioactive seeds into the resection marginby endoscopic surgery. It overcomes the technical difficulties ofmanipulating in the narrow chest cavity. With the advent of robotictechnology, new options in the treatment of lung cancer, as well asother malignant tumors, will become available. However, this is acomplicated and expensive solution.

Other prior art is shown in U.S. Pat. No. 5,906,573 to Aretz and U.S.Pat. No. 6,264,599 to Slater et al. The Aretz '573 patent describes aradioactive surgical fastening instrument in which a radioisotope isincorporated by ion implantation. The Slater et al '599 patent describesradioactive therapeutic seeds which have means for engaging the tissuesurrounding the seeds when the seeds are implanted. Although thesepatents disclose the concept of associating a radioactive source with afastener, none of these prior art references teach incorporating aradioisotope into a fastener that is used in the actual surgicalprocedure, particularly as part of a surgical staple. In, for example,the Slater et al '599 patent they describe the use of an engagementmeans for positioning therapeutic seeds, however, their engagement meansis positioned independent of any surgical operation and is not intendedfor use as a means for conducting any pair of a surgical procedure.

Refer also to our co-pending application Ser. No. 12/462,042 and alsoour issued U.S. Pat. No. 7,604,586, both of which are herebyincorporated by reference herein. They disclose the unique fasteningmeans while the present invention is directed to the means by which thefastening means is applied.

Accordingly, it is an object of the present invention to provide anapparatus or instrument for incorporating a radioactive source into orwith a surgical procedure means such as a surgical staple so that theradioactive source can be positioned substantially concurrently with theapplication of the surgical tissue securing means.

Still another object of the present invention is to provide abrachytherapy source-delivery system and instrument that facilitates theprecise placement of brachytherapy sources relative to a surgicalmargin, assures the seeds remain fixed in their precise position for theduration of the treatment, overcomes the technical difficulties ofmanipulating the seeds through a narrow surgical incision inherent inminimally invasive procedures, and at the same time reduces theradiation dose to the clinicians.

BRIEF SUMMARY OF THE INVENTION

The present invention facilitates the precise placement of, for example,¹²⁵Iodine seeds relative to the surgical margin, assures the seedsremain fixed in their precise position for the duration of thetreatment, overcomes the technical difficulties of manipulating theseeds through the narrow surgical incision, and reduces the radiationdose to the clinicians. The concepts of the present inventionincorporate the radioactive ¹²⁵Iodine seeds into a fastening means,preferably surgical staples, used in the surgical procedure. In thisway, the seeds are concurrently secured in position directly adjacent tothe surgical resection and remain immobile. They are precisely locatedrelative to the resection, placed by a very convenient methodeliminating the difficulties of working through the narrow surgicalincision. The seed position is rigidly fixed, assuring that the dosedistribution does not uncontrollably change over the duration of thetreatment. This method permits the dose distribution to be preciselyplanned prior to the surgery to achieve the desired result. Insertion ofthe seeds in conjunction with the application of the staples alsosignificantly reduces the dose to the clinician.

In accordance with the present invention the source delivery system isused in conjunction with a standard surgical stapling instrument, suchas one that is presently used for video-assisted thoracoscopic surgery(VATS). By integrating a permanent brachytherapy source in a standardsurgical stapling instrument, there is provided a single instrument tocut and seal lung tissue and simultaneously place a permanentradioactive seed implant. With the instrument of the present invention:(1) The source/staple does not compromise the pre-established parametersof standard surgical staple delivery systems; (2) Uses preferably thesame materials, measurements, and spacing of existing surgical staples;(3) Is deliverable using currently available surgical spacinginstruments; (4) Is easily assembled with the standard stapler cartridgeand is readily sterilized; and (5) Can be deliverable with minimalradiation exposure to the physician and other operating-room personnel.

DESCRIPTION OF THE DRAWINGS

Numerous other objects, features and advantages of the present inventionare now realized by a reading of the following detailed descriptiontaken in conjunction with the accompanying drawings, in which:

FIG. 1 is an example of the staple pattern in a typical surgicalstapling system;

FIG. 2 is an illustration of a single staple that is attached with aretaining sleeve that accommodates a radioactive seed;

FIG. 3 is a further example, like that shown in FIG. 2, but using a pairof staples interconnected with a single sleeve;

FIG. 4 illustrates a plan for a single resection, margin with an axiallysymmetric seed;

FIG. 5 illustrates another staple configuration;

FIG. 6 illustrates still another staple configuration;

FIG. 7 is a cross-sectional view of the staple of FIG. 6 showing thestaple closed to join tissue;

FIG. 8 illustrates dose distribution for the embodiment of FIG. 6;

FIG. 9 schematically illustrates another embodiment of the presentinvention;

FIG. 10 schematically illustrates one standard staple array in parallelwith a source array;

FIG. 11 is a perspective view depicting an instrument constructed inaccordance with the principles of the present invention and illustratingside-by-side staple mechanisms; one for applying standard staples andthe other for applying source staples;

FIG. 12 is an enlarged fragmentary perspective view at the distal end ofthe instrument with the staple mechanisms retained by a common holder;

FIG. 13 is an enlarged fragmentary perspective view at the distal end ofthe instrument with the standard staple mechanism actuated;

FIG. 14 is an enlarged fragmentary perspective view at the distal end ofthe instrument with the source staple mechanism actuated;

FIG. 15 is a perspective view of the staple mechanism holder used at thedistal end of the instrument;

FIG. 16 is an enlarged exploded perspective view at the distal end ofthe instrument; and

FIG. 17 schematically illustrates the use of the staple mechanism of thepresent invention in actual use during a surgical procedure such as alung resection.

DETAILED DESCRIPTION

An objective of the present invention is to develop an improved deliverysystem based upon the incorporation of a radioactive seed into fasteningmeans, preferably into a surgical staple. More particularly thedisclosed system is an improved brachytherapy delivery system fortreatment of, inter alia, lung cancer based upon the incorporation ofradioactive ¹²⁵Iodine seeds into surgical staples used in lungresection. For patients with compromised cardiopulmonary status, theinclusion of brachytherapy with sublobular resection has shown asignificant improvement in therapeutic outcome over sublobular resectionalone. This present technique facilitates the delivery of this therapy.Furthermore, the techniques described herein may also be used in othermedical procedures. Moreover, the techniques of the present inventionmay be used in applying other radioactive sources than the specific onesdisclosed herein.

Brachytherapy has the obvious advantage of maximally irradiating thetumor bed while sparing surrounding normal tissue from the field ofradiation. This approach has been especially useful when the requiredradiation dose exceeds the tolerance dose of the surrounding normaltissues. However, logistic issues have limited the application ofbrachytherapy particularly in lung cancer applications.

An objective of the present invention is to develop a simplified methodfor radioactive sources, particularly ¹²⁵Iodine sources, in conjunctionwith the surgical staples used during the resection procedure to permitthe application of brachytherapy at the same time as the surgery isbeing performed. The technique of the present invention facilitates theprecise placement of, for example, ¹²⁵Iodine seeds relative to thesurgical margin, assures the seeds remain fixed in their preciseposition for the duration of the treatment, overcomes the technicaldifficulties of manipulating the seeds through the narrow surgicalincision, and reduces the radiation dose to the clinicians.

This development extends the use of brachytherapy to a much largernumber of compromised lung cancer patients for whom more traditionalsurgical procedures, such as lobectomy, are not an option. Severalstudies have shown the use of radioactive brachytherapy to have aclinical benefit for compromised lung cancer patients for whom moretraditional surgical procedures, such as lobectomy, are not an option.

A preferred embodiment of the present invention demonstrates a morefeasible method for the intraoperative delivery of the ¹²⁵Iodine sourcesin both safety and effectiveness for treatment of lung cancer.

The demonstration of treatment efficacy combined with this improvementin seed delivery encourages the use of this technique for NSCLC patientswith compromised cardiopulmonary status who are not candidates forlobectomy. This development affords the additional clinical benefit ofbrachytherapy to these patients, thereby improving their outcomes. Theimproved dose distribution resulting from more precise sourcepositioning and fixation is expected to improve the currently identifiedclinical benefit of brachytherapy due to the limitations of currenttechniques. Because lung cancer is the leading cause of cancer deaths inthe United States, any improvement in clinical outcome resulting fromthis program translates into significant societal benefit.

These large numbers of prospective patients for this technique also makethis project commercially viable. It is further anticipated that ademonstration of treatment efficacy for lung cancer encourages the useof this radionuclide for brachytherapy of other soft-tissue/small-organcarcinomas where conformal dose distribution around the surgicalresection margin and operator safety are critical. This development forthe improved delivery of ¹²⁵Iodine brachytherapy sources has additionalapplications in brachytherapy. The use of low energy/high activityradiation sources has widespread applications in brachytherapy.

The present invention develops a brachytherapy system that can be usedfor intraoperative placement of radioactive seeds simultaneously withfastener means, preferably surgical staples, used in lung wedgeresection procedures. Such a instrument precisely fixes the position ofthe seeds relative to the resection margin and provide a well defined,stable dose distribution to the target, while facilitating the means fordelivering these seeds with reduced dose to the physicians. In oneembodiment this is performed by having the radiation source integralwith the fastener or staple so that when the resection occurs,concurrently therewith, the radiation source is properly positioned.

The technology of surgical staples and their delivery system is mature.Elements such as wire thickness/diameter, staple length and spacing haveall been designed and validated for their specific purpose. Anymodification to accommodate radioactive ¹²⁵Iodine seeds should avoid anycompromise of these parameters. The design should incorporate currentlyused surgical staples, which are fabricated from wires ranging from 0.21to 0.28 mm diameter, with widths ranging from 3 to 4 mm and leg-lengthsranging from 2.5 to 4.8 mm. These staples are typically spaced ˜1.0 mmapart both longitudinally and laterally, such as shown by the staples Sin the pattern of FIG. 1. The instrument of the present inventionpermits delivery of the seeds and surgical staples usingcurrently-available surgical stapling instruments modified in accordancewith the principles of the present invention. The seed/staplecombination is easily assembled with the staple cartridge. Thecombination is readily sterilizable. The combination is deliverable withminimal radiation exposure to the physician. The design of anyadditional structure around the ¹²⁵Iodine seed should be sensitive toexcessive modulation of the dosimetric parameters of the seed. Refer toFIG. 1 that illustrates an example of the staple pattern in a surgicalstapling system.

One embodiment of a source staple is shown in FIG. 2 and includes theattachment of a sleeve 11 to a single surgical staple 20 by means oflaser welding at 15. The sleeve 10 may be of 0.9 mm OD×0.8 mm ID andaccommodates a standard radioactive ¹²⁵Iodine seed 30, as illustrated inFIG. 2. A standard seed is 4.5 mm long, which is longer than anindividual staple. This could be accommodated in the cartridge in such away as to not interfere with adjacent staples. The radioactive ¹²⁵Iodineseed 30 is inserted and fixed within the sleeve 10. As noted in FIG. 2,the radioactive source and sleeve are preferably symmetrically locatedrelative to the staple 20. FIG. 2 also shows the staple in both a restposition and a released bent position. It is noted that the legs of thestaple are pointed as usual.

An alternative embodiment, as shown in FIG. 3, illustrates theattachment of a sleeve 10 to two adjacent staples 20A and 20B, therebyaccommodating the length and providing an additional measure ofstability. As noted in FIG. 3, the sleeve is preferably symmetricallylocated relative to the pair of staples 20. The sleeve 10 bridgesbetween the adjacently disposed staple pair, secured by means of thelaser weld. The sleeve preferably is in contact with each staple over alike length so as to provide the symmetry. FIG. 3 also shows the staplesin both a rest position and a released bent position.

Other securing means may also be provided to attach the sleeve to thestaple. For example, an adhesive could be used, as long as theattachment location is secure and does not disengage during use. Thus,the system of the present invention provides an integral fastener inwhich the radiation source is integrally formed with the fastener, andusable in a surgical procedure.

Clearly, the addition of stricture around the ¹²⁵Iodine seed modulatesthe dose distribution around the seed. In order to account for this, astudy of the dose distribution around the seed/staple combination issimulated using Monte Carlo techniques.

A full theoretical radiation-dose profile is computed using Monte Carlotechniques for a single ¹²⁵Iodine Seed/Staple Combination to estimateradiation dosimetry at clinical points of interest. The modeledconfiguration includes the structural configuration of the sleeve andstaple, as well as the detailed composition of the ¹²⁵Iodine seeditself. Although the dosimetric parameters of all currently-available¹²⁵Iodine seed have been measured and reported, these parameters will bedifferent by the modulation provided by the sleeve and staple. It isdesired to characterize this specific design to properly plan atreatment.

One element of particular note is that typical brachytherapy seeds andhigh dose rate sources are axially symmetric. The standard formalism fordescribing the dosimetric aspects of these seeds/sources, the Report ofAAPM Task Group 43, is based on the assumption of axial symmetry. Inthis case, due to the location of the staple on one side of the seed,the dose distribution is expected to be axially asymmetric.Consequently, the formalism of AAPM TG-43 is not directly applied, butrather characterized in a 3-D representation.

The Monte Carlo calculation is performed using the MCNP Version 5 MonteCarlo computer code, developed by LANL. The MCNP5 Monte Carlo code is ageneral neutron, photon, and electron radiation transport code thatfacilitates modeling complicated three-dimensional, heterogeneousgeometrical structures such as medical sources and applicators. Thesimulation geometry mimics the geometrical and elemental compositions ofthe source and its surrounding stricture. The spatial resolution of thecomputed dose distribution can be as small as 100 □m. Its photontransport model includes photoelectric effect and accompanyingfluorescence emission, coherent (Thomson) scattering, Compton scatteringand pair production. A continuous-slowing-down model is used forelectron transport that includes positrons, K x-rays and bremsstrahlung.MCNP is the only widely-used radiation transport code that permitscoupled transport of photons, electrons, and neutrons.

The dose distribution is calculated for radial distances ranging from0.5 to 10 cm over polar angles ranging from 0° to 180° and azimuthalangles from 0° to 360°. The calculated dose distribution is deconvolvedinto a 3-D dose kernel for use with our treatment planning system thatconforms as closely as practical with the formalism described by AAPMTG-43. This characterizes the dose rate constant, A, the radial dosefunction, g_(L)(r), and the geometry function, G_(L)(r,θ). However, thischaracterizes a 3-D anisotropy function, F(r,θ,□), rather than the 2-Danisotropy function, F(r,θ), recommended by TG-43.

The dose distribution in the surgical resection target is evaluated forclinical suitability. Studies have specified that the dose delivered toup to 1 cm from the resection margin should be 125-140 Gy. A treatmentwith seed positions is selected to achieve that goal.

In most brachytherapy situations, this treatment plan could be performedusing a standard treatment planning system. FIG. 4 shows a typical planfor a single resection margin using a standard treatment planning systemwith axially symmetric seed dosimetry. However, the I-Plant TPS, as wellas all other commercial treatment planning software assume axiallysymmetric dose distributions in their calculational algorithms.Consequently, standard treatment planning software does not account foraxial asymmetry and therefore does not provide precise results. We willdevelop a modification to our existing Treatment Planning Software toaccommodate the three-dimensional dosimetry kernel for this application.Using this new module, a series of treatment plans are performed toachieve the dose specification. The design objective of the treatment isto deliver a dose of 125-140 Gy to the target region within 1 cm of thesurgical resection margin. This creates an optimized treatment plan tomeet this objective. The adapted treatment planning system is used tooptimize the number and position of seeds within the constraints of theavailable positions within the cartridge.

These treatment plans are dosimetrically evaluated. The treatmentplanning system calculates the implant dose distribution for eachgeometry. A dose-volume histogram (DVH) is constructed from the dosedistribution, and analyzed with respect to the defined volumes. From theDVH, we determine the volume and percent of target volume receiving 100%of the prescription, dose (V₁₀₀), receiving 150% of the prescriptiondose (V₁₅₀), and receiving 200% of the prescription dose (V₂₀₀). We alsocompute the minimum dose received by more than 90% of the target volume(D₉₀) and its relationship to the prescription volume.

Dosimetric quality of the implant is evaluated using criteria includingthe mean central dose (MCD), average peripheral dose (APD), andpercentage deviation between the APD and the prescription dose (DAV).Implants are also evaluated using the dose homogeneity index (DHI),defined as:

${{DH}\; 1} = \frac{V_{100} - V_{150}}{V_{100}}$

The successful treatment plan has MCD, APD and D₉₀ values closest to theprescription dose of 125-140 Gy, the highest DHI, and the lowest V₂₀₀.

From the design criteria being observed for the ¹²⁵Iodine seed/staplecombination, it is intended to make as few modifications to the staplecartridge as are necessary. One criterion that would be inviolate is thepositioning of the staples. Within this constraint, we would make themodifications necessary to the design of the cartridge insert toaccommodate the additional space needed for the seed/sleeve combination.As the number of seeds required are far lower than the number of staplesused, we expect the introduction of seeds will have minimal impact.

The cartridges for the surgical staples may be molded in plastic. Thismaterial does not provide any appreciable shielding, even for such a lowenergy radionuclide as ¹²⁵Iodine. However, high density plasticscontaining tungsten are available and are regularly used for radiationshielding for ¹²⁵Iodine seeds. We would plan to fabricate the specialcartridge using this type of plastic. The cartridge would be designed toprovide adequate shielding for the clinicians handling this instrumentduring the surgical procedure.

Another embodiment in accordance with the present invention is shown inFIG. 5 and includes an integrally formed staple structure shown in bothopen and closed positions. This is comprised of a radioactive centerelement 41 and an encapsulating outer element 42. The ends 44 are shownblunt but in practice would be pointed so as to function as a surgicalstaple. The base of the staple is preferably about 3 inches and eachleg, in the open position is about 2 inches. These can be readilyaccommodated in a conventional staple delivery cartridge.

As mentioned previously, currently-used surgical staples are fabricatedfrom titanium wires ranging from 0.21 to 0.28 mm diameter, with widthsranging from 3 to 4 mm and leg-lengths ranging from 2.5 to 4.8 mm. Thesestaples are typically spaced ˜1.0 mm apart both longitudinally andlaterally, as shown in the pattern of FIG. 1. However, the surgicalstapling instruments used to deliver these staples can accommodatestaples with diameters even as large as 0.50 mm.

Reference is now made to FIG. 6 for an illustration of still anotherembodiment that incorporates the radioactive material inside the stapleitself by sealing it within a cavity created from a titanium tube. InFIG. 6 the staple is shown in both open and closed positions. Refer alsoto FIG. 7 for further details of this staple structure. FIG. 7 alsoillustrates the staple 50 as engaging a tissue 55 at incision 57. Thisstaple 50 includes a cylindrical tube 52 that is preferably a titaniumtube, but may also be of other metal materials. These materials includeplatinum, titanium, nickel-titanium alloys, gold, stainless steel,palladium, silica and alumina. The tube 52 defines a tubular cavity thatis capped/sealed by titanium wires 54 that are laser-welded to the tube.The wires 54 serve as the legs of the staple.

In the embodiment shown in FIGS. 6 and 7 the radioactive material 56 islocated inside the titanium tube which may be of ˜0.40 mm in diameterwith a wall thickness of −0.07 mm, resulting in a cavity of 0.26 mmdiameter. The ends of the tube 52 are plugged with titanium wires 54 of0.25 mm diameter which may be laser-welded to the tubing. These wires 54are typical of the wire-size currently used in surgical staples. Such atubular capsule of 0.40 mm diameter readily fits within the cavity ofcurrently-used staple delivery systems.

One concern with the initial design concept of the source/staple is thedegree to which the addition of asymmetric structure around the¹⁶⁹Ytterbium source modulates the dose distribution. We have made apreliminary assessment of this using the Monte Carlo technique. TheMonte Carlo calculation was performed using the MCNP Version 5 MonteCarlo computer code, developed by LANL (MCNP5). The MCNP5 Monte Carlocode is a general neutron, photon; and electron radiation transport codethat facilitates modeling complicated three-dimensional, heterogeneousgeometrical structures such as medical sources and applicators. Itsphoton transport model includes photoelectric effect and accompanyingfluorescence emission, coherent (Thomson) scattering, Compton scatteringand pair production. A continuous-slowing-down model is used forelection transport that includes positrons, K x-rays and bremsstrahlung.MCNP is the only widely-used radiation transport code that permitscoupled transport of photons, electrons, and neutrons.

The simulation geometry mimicked the geometrical and elementalcompositions of the source/staple and its surroundings. The dosedistribution in water was calculated for a radial distance of onecentimeter in a plane containing the legs of the staple (Y-Z plane) andalso in a plane perpendicular to the plane containing the legs of thestaple (X-Z plane). Dosimetry data were calculated in each of theseplanes over angles ranging from 0° to 360° (in ten degree increments)using the *F8 tally in a 40 cm diameter phantom. Refer to FIG. 8 for twodifferent sources as to their dose distribution at one centimeter fromthe source/staple in the plane containing the legs of the staple (Y-Zplane) and the plane perpendicular (X-Z plane). ¹⁶⁹Ytterbium is shown onthe left and ¹²⁵Iodine is shown on the right.

The dose perturbation by the staple legs in the deployed (bent over)position for ¹⁶⁹Ytterbium is very small (4-5%) and is most predominantat oblique angles in the Y-Z plane (30°-45° and 135°-150°). This is muchless than the perturbation observed for ¹²⁵Iodine in these directions(˜32%). The most significant purterbation occurs along the axis of thesource/staple, which is common for all brachytherapy sources. In thiscase, the perturbation for ¹⁶⁹Ytterbium (19%) is much less than thatobserved for ¹²⁵Iodine (57%). This preliminary dose study shows that theanisotropy resulting from the ¹⁶⁹Ytterbium source/staple issignificantly better that that resulting from the ¹²⁵Iodinesource/staple.

FIG. 9 shows still another embodiment for practicing the presentinvention. Instead of providing the radioactive source within thefastener or staple, in this embodiment there is schematicallyillustrated a series of staples 60 that may each be of conventionaldesign but that have associated therewith a radioactive source shown at62. The staples 60 are shown as associated with a surgical margin orincision 64. The sources 62 are distributed or positioned by means of athe line 66. In an alternate arrangement a loop may be used at 62 andthe line 66 may be a radioactive line supported by the loops 62 or theline 66 may carry spaced radioactive sources.

The concepts of the present invention are described in connection with alung brachytherapy. In this connection reference is made to theschematic diagram of FIG. 17 illustrating a set of stapler instrumentsat 70 that are each respectively engaged through a skin incision. Thisis illustrated in FIG. 17 as between ribs. FIG. 17 also illustrates theconventional video thoracoscope at 72 introduced through anotherincision for viewing the operative site. As indicated previously, thisparticular procedure is described herein in connection with a lung wedgeresection. In this regard refer to our previously issued U.S. Pat. No.7,604,586, the complete contents of which are now hereby incorporated byreference herein. Before discussing the particular stapler constructionof the present invention, reference is now made to FIG. 10 for anillustration of the staple patterns. This includes a first pattern ofthree rows of standard staples at 74. This array of standard staples at74 is disposed along the cut tissue edge 78. The lung tissue is internalas at 76 in FIG. 10. The source staples are also illustrated in FIG. 10at 75 in a row of two parallel arranged sets of staples. It is notedthat the staple array 75 is substantially in parallel to the staplearray 74. To provide optimum brachytherapy application, it is noted thatthe source array 75 is closest to the lung tissue 76.

Reference is now made to a surgical stapling instrument 80 illustratedin FIG. 11 as in accordance with the present invention. This sourcedelivery system is used in conjunction with a standard surgical staplingapparatus. By integrating a permanent brachytherapy source inassociation with a standard surgical stapling instrument, there isprovided a single instrument that can cut and seal lung tissue andsimultaneously place a permanent radioactive seed implant. In thedescription, even though reference is made to a procedure relating to alung resection, it is noted that the principles of the present inventionmay be applied to any one of a variety of different surgical procedures.The instrument 80 in FIG. 11 illustrates this dual purpose use in asingle instrument.

In FIG. 11 the instrument 80 is comprised of a handle body 82 with afixed handle 85 and a pair of staple cartridge actuators 86 and 87. Thebody 82 is coupled by means of the instrument shaft 84 to the endeffector 83. FIG. 11 also illustrates a holder 88 for retaining the twoseparate staple cartridges described in further detail in FIGS. 12-16.As substantial portions of the stapling mechanism illustrated herein areconsidered of conventional design, reference is now made to existingstaplers for further details of the mechanisms used. For further detailsof stapling mechanisms refer to the following U.S. patents all of whichare hereby incorporated by reference herein: U.S. Pat. No. 5,014,899;U.S. Pat. No. 5,542,594; U.S. Pat. No. 7,540,872 and U.S. Pat. No.7,799,028. Basically, these devices operate on the basis of having aproximal actuator, such as one of the actuators 86 and 87 in FIG. 11herein, operate distal staple application mechanisms which typicallyinclude a cartridge of staples. One of these packages holds standardstaples while the other cartridge holds source staples adjacent thereto.

FIG. 12 is a perspective view at the very distal end of the stapleinstrument with the end effector 83 being comprised of separate butcommonly held (holder 88) staple mechanisms 90 and 91. Associated withthe staple mechanism 90 is actuator arm 96 and associated with thestaple mechanism 91 is the actuation arm 97. In further connection withFIG. 11, the actuation lever 86 operates the actuation arm 96 andseparately the actuation lever 87 operates the actuation arm 97. Each ofthe staple mechanisms 90 and 91 may be comprised of a body and acartridge that holds multiple staples. These staples are illustrated in,for example, FIGS. 12-14. The standard staples are shown at 74 and thesource staples at 75. In this particular instrument, there areside-by-side arrays of two sets of standard staples. Each set includesthree rows of staples. For the source staples, there are two parallelrows of staples. The number of rows may be changed depending upon theparticular surgical procedure. In addition to the actuator arms 96 and97, there are typically provided associated anvils (not shown) forclosing each of the staples. Further details of these staplingmechanisms are found in the aforementioned U.S. patents which are herebyincorporated by reference herein.

FIG. 12 illustrates the side-by-side arrangement of the staplermechanisms 90 and 91 held within the holder 88. Refer also to theperspective view of FIG. 15 which shows the holder 88 having a channel94 for receiving the mechanism 90 and a channel 95 for receiving themechanism 91. In the perspective view of FIG. 12, it is noted that thestandard staple array is disposed on the inner side of the source staplearray. In another arrangement, and depending upon the particularsurgical procedure, these arrays may be alternated in position so thatthe standard staple array is outside of the source staple array. Therelative placement between these two arrays is a function of the desiredside that the source staples are being placed in relationship to thestandard surgical staples.

FIG. 13 illustrates the actuation arm 96 being actuated (depressed) fromthe actuation lever 86 for applying standard staples. Similarly, in FIG.14 the actuation arm 97 is shown actuated from the actuation lever 87for the application of source staples. This action provides a pattern aspreviously identified in FIG. 10 herein.

Reference is now also made to FIG. 16 that is an exploded perspectiveview illustrating the stapling mechanisms 90 and 91 as well as theholder 88. In FIG. 16 it is noted that there may actually be providedtwo separate instrument shafts 84A and 84B. These shafts typicallyretain a cable operated from the handle end (respective actuators 86 and87) of the instrument for controlling the respective actuator arms 96and 97.

The stapling sequence, particularly between standard and source staples,can be performed in a number of different ways. Usually, the standardstaples are first applied followed by the application of the sourcestaples. However, it is also possible to provide concurrent leveractuation so that a source staple is applied at the same time as thestandard staple. In a preferred technique, the instrument progressesalong the surgical margin closing the tissue. Once a set of staples hasbeen fastened in the pattern previously described, then the surgeon canbasically progress along the same path applying the therapeutic sourcestaples with the same basic instrument but actuating the source staplepart of the end effector. Thereafter, the stapling instrument may bemoved to a different location and this type of dual action repeated.

Having now described a limited number of embodiments of the presentinvention, it should be apparent to those skilled in the art thatnumerous embodiments and modifications thereof are contemplated asfalling within the scope of the present invention as defined by theappended claims.

1. An instrument used for brachytherapy delivery in the treatment ofcancer by radiation therapy, said instrument comprising: a handle havingfirst and second handle actuators; an end effector; an instrument shaftthat connects the handle with the end effector; said end effectorcomprised of first and second adjacent disposed cartridges that eachretain a set of staples; said first cartridge for holding standardstaples in a first array, and dispensing said standard staples undercontrol of the corresponding first handle actuator; said secondcartridge for holding radioactive source staples in a second array, anddispensing said radioactive source staples under control of thecorresponding second handle actuator; and a holder for receiving saidfirst and second cartridges in a substantially parallel array so thatthe standard staples close the incision at a surgical margin while thesource staples are secured adjacent thereto.
 2. The instrument of claim1 wherein said radioactive source staple array with each stapleincluding a base and tissue piercing ends and a radioactive source, saidbase formed as a tubular cavity for receiving and holding saidradioactive source therein, and said tissue piercing ends formed as legsof the staple.
 3. The instrument of claim 1 wherein both of said arraysof staples are disposed spaced both longitudinally and laterally.
 4. Theinstrument of claim 1 wherein said staples are constructed of any one ofplatinum, titanium, nickel-titanium alloys, gold, stainless steel,palladium, silica and alumina.
 5. The instrument of claim 1 wherein saidstaple ends form pointed legs of wire having a diameter between 0.21 mmand 0.5 mm, leg widths ranging from 3 mm to 4 mm, and leg lengthsranging from 2.5 mm to 4.8 mm.
 6. The instrument of claim 1 wherein thestaples of both arrays are spaced apart about 1.0 mm both longitudinallyand laterally.
 7. The instrument of claim 1 wherein said staples eachhave base that includes a sleeve and said radioactive source includes aradioactive seed, said sleeve accommodating said radioactive seed. 8.The instrument of claim 7 wherein the radioactive seed is an iodineseed, and said sleeve is a tubular sleeve.
 9. The instrument of claim 7wherein said sleeve is a tubular sleeve having an outer diameter on theorder of 0.9 mm and an inner diameter on the order of 0.8 mm.
 10. Theinstrument of claim 9 wherein the radioactive seed is an iodine seedhaving a length on the order of 4.5 mm.
 11. The instrument of claim 1wherein said standard staples are positionable for piercing said tissuein performing a surgical procedure at a surgical margin whilesubstantially concurrently said source staples secure said radioactivesource in a fixed position at said surgical margin.
 12. The instrumentof claim 11 wherein said array of source staple is constructed andarranged to extend spaced longitudinally of the surgical margin.
 13. Theinstrument of claim 1 wherein the staples of at least one array arefabricated from wires ranging from 0.21 to 0.28 mm diameter, with widthsranging from 3 to 4 mm and leg-lengths ranging from 2.5 to 4.8 mm. 14.The instrument of claim 1 including a pair of staples of at least onearray that are arranged to be secured by a common sleeve that extendstherebetween.
 15. The instrument of claim 1 wherein said tubular cavityis formed by an encapsulating outer element, and said radioactive sourceincludes a radioactive center element, said outer element encapsulatingsaid radioactive center element.
 16. The instrument of claim 1 whereinthe tubular cavity is formed by a metal tube.
 17. The instrument ofclaim 16 wherein the metal tube is one of platinum, titanium,nickel-titanium alloys, gold, stainless steel, palladium, silica andalumina.
 18. The instrument of claim 16 wherein the metal tube is on theorder of 0.40 mm in diameter, with a wall thickness on the order of 0.07mm, resulting in a cavity of on the order of 0.26 mm diameter.
 19. Theinstrument of claim 18 including metal wires engaged with the metaltube.
 20. The instrument of claim 19 wherein the wires are titaniumwires having a diameter on the order of 0.25 mm and laser welded to themetal tube.
 21. The instrument of claim 1 wherein the radioactive sourceis for cancer treatment and is characterized by a dose distributiondelivery of 125-140 Gy within 1 cm of the instrument.
 22. The instrumentof claim 21 wherein the standard staples are applied followed byapplying the source staples.
 23. The instrument of claim 22 wherein acomplete line of standard staples are applied followed by a completeline of source staples.
 24. An instrument used as a brachytherapydelivery means in the treatment of cancer by radiation therapy, saidapparatus comprising: a control handle; an end effector; an instrumentshaft that connects the control handle with the end effector; said endeffector comprised of first and second adjacently disposed cartridgesthat each retain a set of staples; said first cartridge for holdingstandard staples in a first array, and dispensing said standard staplesunder operation from said control handle; said second cartridge forholding radioactive source staples in a second array; said sourcestaples each comprised of a base, tissue piercing ends, a radioactivesource, and means for mounting the radioactive source to the base; saidsecond cartridge for dispensing said source staples under operation fromsaid control handle; said cartridges for retaining and selectivelyapplying the staples along a surgical margin so that the standardstaples close the incision at a surgical margin while the source staplesare secured adjacent thereto.
 25. The instrument of claim 24 including adistal holder for retaining the first and second cartridges in asubstantially parallel array.
 26. The instrument of claim 25 whereineach cartridge control handle also has respective first and secondhandle actuators for controlling the application of staples.
 27. Theinstrument of claim 24 wherein said base is formed by a tubular cavity,and said radioactive source includes a radioactive center elementdisposed in said tubular cavity.
 28. The instrument of claim 27 whereinthe tubular cavity is formed by a metal tube.
 29. The instrument ofclaim 28 wherein the metal tube is one of platinum, titanium,nickel-titanium alloys, gold, stainless steel, palladium, silica andalumina.
 30. The instrument of claim 24 wherein said source staples fixthe position of the radioactive source relative to the surgical martinto provide a stable dose distribution thereat.